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首页> 外文期刊>Journal of cellular physiology. >SMARCD1 is a transcriptional target of specific non-hotspot mutant p53 forms
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SMARCD1 is a transcriptional target of specific non-hotspot mutant p53 forms

机译：SMARCD1是一个转录特定的目标non-hotspot p53突变形式

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摘要

Though primarily a tumor suppressor, TP53 harboring specific missense mutations located in the region encoding the DNA binding domain exhibits a gain of function by transcriptional activation of oncogenes. We performed microarray-based messenger RNA profiling of squamous cell carcinoma of the oral tongue (SCCOT) and identified significant elevation of SMARCD1 in samples exhibiting p53 nuclear stabilization. Activation of SMARCD1 by mutant p53 was confirmed by evaluation of additional tongue cancer samples as well as The Cancer Genome Atlas expression datasets. SMARCD1 knockdown in HNSCC cells resulted in a significant reduction in several tumorigenic characteristics including cell viability, ability to form colonies in liquid and solid media and cell migration. We identified significantly increased SMARCD1 transcript levels in tumor versus matched normal samples in SCCOT as well as in other cancer types. Increased SMARCD1 expression predicted poor survival in HNSCC tumors harboring missense p53 mutations. Our results suggest SMARCD1 to be a novel transcriptional target of mutant p53.
机译：虽然主要是一个肿瘤抑制,TP53窝藏位于特定的错义突变该地区编码DNA结合域展览增加转录的功能致癌基因的激活。芯片信使核糖核酸的分析口腔鳞状细胞癌的舌(SCCOT)和识别重要的海拔SMARCD1样本中表现出p53核稳定。证实了p53评估额外的舌癌样本以及癌症基因组图谱表达数据集。在HNSCC细胞导致击倒在几个肿瘤发生的显著减少特征包括细胞生存能力,能力在液体和固体媒体和形式的殖民地细胞迁移。增加了肿瘤的SMARCD1转录水平在SCCOT以及与匹配正常样本在其他类型的癌症。表达预测HNSCC贫困生存p53肿瘤窝藏错义突变。结果表明SMARCD1小说转录变异p53的目标。

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